STEP 1 demonstrated that once-weekly semaglutide 2.4 mg produced a mean weight reduction of 14.9% compared with 2.4% with placebo in adults with obesity without type 2 diabetes, with a third of participants losing more than 20% of body weight, setting a new benchmark for pharmacological weight management and preceding the cardiovascular outcomes evidence from SELECT.
Browsing: Therapeutics
Drug-class and individual-agent evidence: GLP-1 receptor agonists, SGLT2 inhibitors, and the major trials behind semaglutide, tirzepatide, and related therapies.
The REWIND trial demonstrated that dulaglutide reduces 3-point MACE in a broad type 2 diabetes population of which 69% had no established cardiovascular disease, with a significant 24% reduction in nonfatal stroke and consistent renal benefit, extending GLP-1 receptor agonist cardiovascular protection into a primary prevention context.
The SUSTAIN-6 trial demonstrated that once-weekly semaglutide reduced 3-point MACE by 26% in high-cardiovascular-risk type 2 diabetes, driven primarily by a significant 39% reduction in nonfatal stroke, while identifying a retinopathy complication signal attributable to rapid glucose lowering in patients with pre-existing retinopathy.
The LEADER trial demonstrated that liraglutide significantly reduced 3-point MACE and cardiovascular mortality in patients with type 2 diabetes and high cardiovascular risk, becoming the first GLP-1 receptor agonist CVOT to demonstrate superiority and characterising an atherosclerotic rather than heart failure protection profile distinct from SGLT2 inhibitors.
DAPA-CKD demonstrated that dapagliflozin reduced the composite of a sustained 50% or greater eGFR decline, end-stage kidney disease, or renal or cardiovascular death by 39% in patients with albuminuric CKD with or without type 2 diabetes, extending nephroprotective SGLT2 inhibition beyond diabetic nephropathy to a broad CKD population for the first time.
EMPEROR-Reduced confirmed that empagliflozin reduces cardiovascular death or hospitalisation for heart failure by 25% in patients with HFrEF irrespective of diabetes status, while also demonstrating a 50% reduction in a renal composite outcome and a markedly slower rate of eGFR decline, adding critical confirmatory evidence for SGLT2 inhibitors as standard-of-care in HFrEF.
The DAPA-HF trial demonstrated that dapagliflozin reduced the composite of worsening heart failure or cardiovascular death by 26% in patients with heart failure and reduced ejection fraction, with consistent benefit observed in both those with and without type 2 diabetes, establishing SGLT2 inhibition as a core therapy for HFrEF independent of glycaemic status.
A biomarker substudy finds empagliflozin modulates sirtuins and microRNAs after myocardial infarction, with a panel predicting recovery. PICO summary and expert commentary.
A 20-week RCT finds empagliflozin improves nerve conduction velocity in diabetic neuropathy but not clinical exam scores, with glycaemic confounding. PICO summary and commentary.
The CREDENCE trial demonstrated that canagliflozin reduced the composite of end-stage kidney disease, doubling of serum creatinine, or renal or cardiovascular death by 30% in patients with type 2 diabetes and albuminuric chronic kidney disease, becoming the first dedicated renal outcomes trial to demonstrate that an SGLT2 inhibitor could substantially slow the progression of diabetic nephropathy.